Episodic memories, particularly those associated with stressful experiences, often persist throughout a lifetime. While extensive research has helped us to better understand the hippocampal mechanisms mediating the formation of episodic memories, the role of the cortex is less well understood. Our project seeks to establish the contribution of the retrosplenial cortex (RSC), and its interactions with the dorsal hippocampus (DH), to the encoding, consolidation, and retrieval of contextual fear-provoking memories. We propose that RSC, by integrating dorsohippocampal (DH) inputs, plays a principal role in the processing of contextual memories from the earliest stages of memory encoding to remote retrieval, but that RSC, rather than DH, is the gateway of information to other parts of the neocortex. We also posit that three distinct DH-RSC projections contribute to the formation, recent, and remote retrieval of context memories, whereas layer 5 RSC neurons contribute to long-term memory consolidation. Our approaches will consist of conditional genetic and chemogenetic manipulations of individual RSC neuronal populations as well as DH-RSC projections. This will be complemented by optogenetic-electrophysiological approaches of the functional neuroanatomy of DH-RSC projections and RSC layer-specific analyses of immediate early gene responses related to memory. Understanding the molecular and circuit mechanisms of RSC function as they relate to memory will inform the development of novel treatment approaches for cognitive deficits in patients suffering from neurological and psychiatric disorders. Ideally, our findings will identify cortical pathways whose stimulation can bypass the requirement for the hippocampus in memory formation and can thus serve as a novel treatment option.

Public Health Relevance

We propose to establish the mechanisms by which the retrosplenial cortex contributes to the formation, retrieval, and lasting storage of stress-related episodic memories. Our experiments are designed to identify cortical circuits whose stimulation can bypass the requirement for the hippocampus in memory processing and might thus serve as a novel treatment option in patients with cognitive and affective disorders.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Neurobiology of Learning and Memory Study Section (LAM)
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Vicentic, Aleksandra
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Northwestern University at Chicago
Schools of Medicine
United States
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Corcoran, Kevin A; Yamawaki, Naoki; Leaderbrand, Katherine et al. (2018) Role of retrosplenial cortex in processing stress-related context memories. Behav Neurosci 132:388-395
Radulovic, Jelena; Ren, Lynn Y; Gao, Can (2018) N-Methyl D-aspartate receptor subunit signaling in fear extinction. Psychopharmacology (Berl) :
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Radulovic, Jelena (2017) Using New Approaches in Neurobiology to Rethink Stress-Induced Amnesia. Curr Behav Neurosci Rep 4:49-58
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Corcoran, Kevin A; Frick, Brendan J; Radulovic, Jelena et al. (2016) Analysis of coherent activity between retrosplenial cortex, hippocampus, thalamus, and anterior cingulate cortex during retrieval of recent and remote context fear memory. Neurobiol Learn Mem 127:93-101
Leaderbrand, Katherine; Chen, Helen J; Corcoran, Kevin A et al. (2016) Muscarinic acetylcholine receptors act in synergy to facilitate learning and memory. Learn Mem 23:631-638
Yamawaki, Naoki; Radulovic, Jelena; Shepherd, Gordon M G (2016) A Corticocortical Circuit Directly Links Retrosplenial Cortex to M2 in the Mouse. J Neurosci 36:9365-74